Water soluble active ingredients that are susceptible to degradation in the presence of water are difficult to formulate. A major challenge in the development of topical compositions of these water soluble and water susceptible active ingredients lies in maintaining their physico-chemical stability. This is because such drugs are unstable in solution form and are sensitive to water, light, moisture and protic solvents. Further, the oxidative processes are also responsible for destabilizing many of these active agents in formulations leading to physico-chemical instability.
Since the drugs are susceptible to hydrolysis, topical compositions comprising aqueous phase or polar solvent are not feasible due to drug instability. Further, in case of non-aqueous composition, the penetration of a water soluble active ingredient becomes a major concern in that the composition do not show proper therapeutic effect upon topical application, due to lack of absorption or penetration.
There remains a medical need for a stable, commercially feasible, easy to manufacture and easy to use topical composition of a water soluble, water susceptible active drug which on one hand is physically and chemically stable for the duration of its shelf life and on the other hand show optimum drug bio-availability and efficacy upon topical application. The present invention fulfills this need. The present inventors have surprisingly found a solution to the aforesaid problems by providing a nanoparticulate topical composition of a water soluble and water susceptible active ingredient which is physically and chemically stable. It was surprisingly observed that in the nanoparticulate topical composition developed by the present inventors, the active ingredient remained stable inspite of undergoing nanosizing, which otherwise result in formation of impurities. The present inventors have also discovered that compositions containing nanoparticles of minocycline or its pharmaceutically acceptable salts, a water soluble and water susceptible active agent, provide an improved efficacy.